5-Methoxy-1-methyl-2-((E)-styryl)-1H-indole | 117616-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-Methoxy-1-methyl-2-((E)-styryl)-1H-indole
• 英文别名: 5-methoxy-1-methyl-2-(2-phenylethenyl)indole
• CAS: 117616-08-7
• 化学式: C₁₈H₁₇NO
• 分子量: 263.339
• InChiKey: GPPHJDDYAIFYRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  14.16
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  5-Methoxy-1-methyl-2-((E)-styryl)-1H-indole 在 manganese(IV) oxide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 42.0h， 生成 9-methoxy-6-methyl-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

  摘要：

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

  DOI：

  10.1021/jm0512591
• 作为产物：
  描述：

  2-trimethylsilylmethyl-4-anisidine 在 sodium hydride 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 5-Methoxy-1-methyl-2-((E)-styryl)-1H-indole
  参考文献：
  名称：

  的分子内Peterson烯邻-trimethylsilylmethyl酰苯胺：一种新的合成Ñ -methylindoles

  摘要：

  据报道，在温和的条件下，通过邻-三甲基甲硅烷基甲基苯甲酸酯的环化反应，对吲哚进行了改进的马德隆合成吲哚。

  DOI：

  10.1039/c39880000807

文献信息

• The Enantioselective, Organocatalyzed Diels-Alder Reaction of 2-Vinylindoles with α,β-Unsaturated Aldehydes: An Efficient Route to Functionalized Tetrahydrocarbazoles
  作者：Changwu Zheng、Yingpeng Lu、Junkang Zhang、Xingkuan Chen、Zhuo Chai、Wenying Ma、Gang Zhao

  DOI：10.1002/chem.201000130

  日期：2010.5.25

  Prolinol catalysts: A highly enantio‐ and diastereoselective prolinol‐catalyzed Diels–Alder reaction of 2‐vinylindoles and α,β‐unsaturated aldehydes is developed (see scheme). This methodology allows the development of further applications of prolinols in asymmetric synthesis. The resulting densely functionalized enantiomerically pure tetrahydrocarbazoles are useful in the total synthesis of natural

  脯氨醇催化剂：开发了2-乙烯吲哚和α，β-不饱和醛的高度对映异构和非对映异构选择性的脯氨醇催化的Diels-Alder反应（参见方案）。这种方法学可以进一步发展脯氨醇在不对称合成中的进一步应用。所得的密集官能化的对映体纯的四氢咔唑可用于天然产物的全合成，如阿瓜米林生物碱长春花碱的核心结构。
• Organocatalytic Diels-Alder Reaction of 2-Vinylindoles with Methyleneindolinones: An Efficient Approach to Functionalized Carbazolespirooxindoles
  作者：Lin-Jie Huang、Jiang Weng、Sheng Wang、Gui Lu

  DOI：10.1002/adsc.201400780

  日期：2015.3.23

  An unprecedented asymmetric Diels–Alder reaction of 2‐vinylindoles with methyleneindolinones has been disclosed. Under bifunctional organocatalysis by cinchona‐derived squaramide catalyst, a series of diversely functionalized carbazolespirooxindole derivatives bearing three contiguous stereocenters are rapidly constructed under mild conditions (48–90% yields, up to >20:1 dr and 99% ee).

  已经公开了前所未有的2-乙烯基吲哚与亚甲基吲哚满酮的不对称Diels-Alder反应。在金鸡纳酸衍生的方酰胺催化剂的双功能有机催化下，在温和的条件下（48-90％的收率，高达> 20：1 dr和99％ee的情况下），可以快速构建一系列具有三个连续的立体中心的多种官能化的咔唑螺氧并恶唑衍生物。
• 4-Phenylpyrrolo[3,4-<i>c</i>]carbazole-1,3(2<i>H</i>,6<i>H</i>)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution
  作者：Brian D. Palmer、Andrew M. Thompson、R. John Booth、Ellen M. Dobrusin、Alan J. Kraker、Ho H. Lee、Elizabeth A. Lunney、Lorna H. Mitchell、Daniel F. Ortwine、Jeff B. Smaill、Leesa M. Swan、William A. Denny

  DOI：10.1021/jm0512591

  日期：2006.8.1

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.
• Intramolecular peterson olefination of ortho-trimethylsilylmethyl anilides: a new synthesis of N-methylindoles
  作者：Giuseppe Bartoli、Marcella Bosco、Renato Dalpozzo、Paolo E. Todesco

  DOI：10.1039/c39880000807

  日期：——

  A modified Madelung synthesis of indoles by cyclisation of ortho-trimethylsilylmethyl anilides under mild conditions is reported.

  据报道，在温和的条件下，通过邻-三甲基甲硅烷基甲基苯甲酸酯的环化反应，对吲哚进行了改进的马德隆合成吲哚。